The aim of this program is to study the physical determinants of lung parenchymal function. We view lung parenchyma as a structure in which gas transport, elasticity, and hysteresis arise from physical properties controlling the configuration, mechanical stability, and efficacy of gas exchanging surfaces and small airways serving them. Static equilibrium and dynamic stability of parenchymal structures and hence lung function, are based in the nature of bounding structures, the connective tissue matrix, the gas-liquid interface, and their mechanical interactions. In turn, thes are governed by physiological processes controlling the molecular composition and the cellular microenvironment. Derangements of these processes alter structure and composition, and hence lung function. The goal of this program is to investigate newly discovered biophysical mechanisms that form the basis of lung function at each of these levels, th connections between levels, and the changes that occur in biologically important departures from the normal state. Our approach is multidisciplinary, involving investigators knowledgeable in respiratory physiology, physics, engineering mechanics, and biology of chemical mediators, thoracic disease, cell biology, mathematics, and computer science. Collective, the projects of this program address the cascade of events that culminate in normal or abnormal architecture, mechanics and gas transport.